The inherited blood coagulation disorder hemophilia A results from deficiency in the expression or function of FVIII. The MiniAdF VIII vector is a "gutless" adenovirus vector designed to restore production of human FVIII by delivering the entire FVIII cDNA to somatic cells. Nonclinical pharmacology, toxicology and biodistribution studies have been performed. Importantly, physiological levels of FVIII were produced in vivo, and these levels persisted for an extended period of time, resulting in phenotypic correction in hemophilic mice and dogs. The objective of this clinical study is to evaluate through dose escalation the safety of intravenous infusion of MiniAdFVIII vector in severe hemophilia A patients without inhibitors. Additional objectives of this study are as follows: (1) to evaluate through dose escalation the ability of an intravenous infusion of MiniAdFVIlI vector to produce circulating, functional levels of FVIII, (2) to evaluate the effect of MiniAdFVIIl vector therapy on the frequency and severity of bleeding events following defined dose escalation, (3) to evaluate immunologic responses following the administration of MiniAdF VIII vector by monitoring anti-adenoviral and anti-FVIII antibody titers in blood, and (4) to determine the functional FVIII expression profile by measuring the level, time course, and duration of functional and circulating FVIII. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE